Single-cell analysis of human ovarian cortex identifies distinct cell populations but no oogonial stem cells

被引:240
作者
Wagner, Magdalena [1 ,2 ]
Yoshihara, Masahito [3 ]
Douagi, Iyadh [4 ,11 ]
Damdimopoulos, Anastasios [5 ]
Panula, Sarita [1 ,2 ]
Petropoulos, Sophie [1 ,2 ,6 ]
Lu, Haojiang [1 ,2 ]
Pettersson, Karin [1 ,2 ]
Palm, Kerstin [1 ,2 ,7 ]
Katayama, Shintaro [3 ]
Hovatta, Outi [1 ,2 ]
Kere, Juha [3 ,8 ,9 ]
Lanner, Fredrik [1 ,2 ,10 ]
Damdimopoulou, Pauliina [1 ,2 ]
机构
[1] Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Obstet & Gynecol, Stockholm, Sweden
[2] Karolinska Univ Hosp, Stockholm, Sweden
[3] Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden
[4] Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, Stockholm, Sweden
[5] Karolinska Inst, Bioinformat & Express Anal Core Facil, Stockholm, Sweden
[6] Univ Montreal, CHUM, Ctr Rech, Dept Med, Montreal, PQ, Canada
[7] Visby Hosp, Dept Gynecol & Obstet, Visby, Sweden
[8] Folkhalsan Res Inst, Helsinki, Finland
[9] Univ Helsinki, Stem Cells & Metab Res Program, Helsinki, Finland
[10] Karolinska Inst, Ming Wai Lau Ctr Reparat Med, Stockholm Node, Stockholm, Sweden
[11] NIAID, Flow Cytometry Sect, Res Technol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
基金
瑞典研究理事会; 日本学术振兴会; 欧盟地平线“2020”;
关键词
ACTIVE GERM-CELLS; TISSUE CRYOPRESERVATION; ADULT HUMAN; LOCALIZATION; FOLLICLES; GENE; VASA; PRESERVATION; TRANSITION; INJECTION;
D O I
10.1038/s41467-020-14936-3
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The human ovary orchestrates sex hormone production and undergoes monthly structural changes to release mature oocytes. The outer lining of the ovary (cortex) has a key role in defining fertility in women as it harbors the ovarian reserve. It has been postulated that putative oogonial stem cells exist in the ovarian cortex and that these can be captured by DDX4 antibody isolation. Here, we report single-cell transcriptomes and cell surface antigen profiles of over 24,000 cells from high quality ovarian cortex samples from 21 patients. Our data identify transcriptional profiles of six main cell types; oocytes, granulosa cells, immune cells, endothelial cells, perivascular cells, and stromal cells. Cells captured by DDX4 antibody are perivascular cells, not oogonial stem cells. Our data do not support the existence of germline stem cells in adult human ovaries, thereby reinforcing the dogma of a limited ovarian reserve. The outer lining or cortex of the human ovary determines fertility and has been postulated to contain oogonial stem cells. Here, the authors generate a single-cell map of the adult human ovarian cortex and show that DDX4 labels perivascular cells but no oogonial stem cells.
引用
收藏
页数:15
相关论文
共 64 条
[31]   Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts [J].
Kumar, Akhilesh ;
D'Souza, Saritha Sandra ;
Moskvin, Oleg V. ;
Toh, Huishi ;
Wang, Bowen ;
Zhang, Jue ;
Swanson, Scott ;
Guo, Lian-Wang ;
Thomson, James A. ;
Slukvin, Igor I. .
CELL REPORTS, 2017, 19 (09) :1902-1916
[32]   Autologous mitochondrial transfer as a complementary technique to intracytoplasmic sperm injection to improve embryo quality in patients undergoing in vitro fertilization-a randomized pilot study [J].
Labarta, Elena ;
Jose de los Santos, Maria ;
Herraiz, Sonia ;
Jose Escriba, Maria ;
Marzal, Alicia ;
Buigues, Anna ;
Pellicer, Antonio .
FERTILITY AND STERILITY, 2019, 111 (01) :86-96
[33]  
Li L, 2017, CELL STEM CELL, V20, P858, DOI 10.1016/j.stem.2017.03.007
[34]   Transgender Men Who Experienced Pregnancy After Female-to-Male Gender Transitioning [J].
Light, Alexis D. ;
Obedin-Maliver, Juno ;
Sevelius, Jae M. ;
Kerns, Jennifer L. .
OBSTETRICS AND GYNECOLOGY, 2014, 124 (06) :1120-1127
[35]   Oocyte development, meiosis and aneuploidy [J].
MacLennan, Marie ;
Crichton, James H. ;
Playfoot, Christopher J. ;
Adams, Ian R. .
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2015, 45 :68-76
[36]   Implications and Current Limitations of Oogenesis from Female Germline or Oogonial Stem Cells in Adult Mammalian Ovaries [J].
Martin, Jessica J. ;
Woods, Dori C. ;
Tilly, Jonathan L. .
CELLS, 2019, 8 (02)
[37]   Initial and cyclic recruitment of ovarian follicles [J].
McGee, EA ;
Hsueh, AJW .
ENDOCRINE REVIEWS, 2000, 21 (02) :200-214
[38]   Vasa homolog genes in mammalian germ cell development [J].
Noce, T ;
Okamoto-Ito, S ;
Tsunekawa, N .
CELL STRUCTURE AND FUNCTION, 2001, 26 (03) :131-136
[39]   Phase Transition of a Disordered Nuage Protein Generates Environmentally Responsive Membraneless Organelles [J].
Nott, Timothy J. ;
Petsalaki, Evangelia ;
Farber, Patrick ;
Jervis, Dylan ;
Fussner, Eden ;
Plochowietz, Anne ;
Craggs, Timothy D. ;
Bazett-Jones, David P. ;
Pawson, Tony ;
Forman-Kay, Julie D. ;
Baldwin, Andrew J. .
MOLECULAR CELL, 2015, 57 (05) :936-947
[40]   Oogonial Precursor Cell-Derived Autologous Mitochondria Injection to Improve Outcomes in Women With Multiple IVF Failures Due to Low Oocyte Quality: A Clinical Translation [J].
Oktay, Kutluk ;
Baltaci, Volkan ;
Sonmezer, Murat ;
Turan, Volkan ;
Unsal, Evrim ;
Baltaci, Aysun ;
Aktuna, Suleyman ;
Moy, Fred .
REPRODUCTIVE SCIENCES, 2015, 22 (12) :1612-1617